1. Field of the Invention
The present invention relates to coccidiosis strains, microbiological cultures comprising such strains, vaccines based thereon, use of such strains for the preparation of such vaccines and methods for the preparation of such vaccines.
2. State of the Art
Coccidiosis is a highly contagious disease that has been known for a long time. Coccidiosis is known to occur in many economically important animal species, such as chickens, cattle, sheep, rabbits, goats, and turkeys. The causative agent of this disease is a parasite of the genus Eimeria. This parasite is a member of the coccidia. Poultry coccidiosis, in particular, is a problem world wide. High stocking densities and specific housing conditions in the modern poultry industry facilitate the spread of coccidia, as there is little or no separation between animals and fecal matter. Since the oocysts are extremely resistant, surviving even partial desiccation, bleaching, and chemical treatment with most disinfectants, it is extremely difficult to avoid environmental contamination with oocysts.
The parasites cause an enteritis in the gut in general, more specifically in poultry. The infection severely attacks the epithelium of the intestines. Therefore, the first clinical signs of infection with the parasite are, e.g., diarrhea. Later in infection, a broader scale of clinical signs becomes manifest, including reduced food intake, malabsorption, decrease in feed conversion efficiency, and reduced weight gain. In the worst case, the infection is lethal. Gregory M W “Pathology of coccidial infections,” Coccidiosis of man and domestic animals (Ed.: P. L. Long) CRC Press, Boca Raton, Fla. Pp. 235-261 (1990); Ruff M D “Pathophysiology and coccidial infections,” Coccidiosis of man and domestic animals (Ed.: P. L. Long) CRC Press, Boca Raton, Fla. Pp. 263-280(1990). Even when the infection develops non-lethally and the animal recovers, the economic losses due to reduced weight gain are large world wide, especially in the many countries where poultry is an important food source. Costs involved in controlling the disease are estimated to exceed USD $600,000,000 yearly.
Apart from factors such as housing conditions, general state of health, age, immune status and genetic make-up of the host, the degree of pathogenicity depends primarily on the Eimeria species. Ruff, M. D., Proceedings of the VIthInternational Coccidiosis Conference (Eds.: J. R. Barta and M. A. Fernando) Moffit Print Craft Ltd., Guelph. Pp. 73-79 (1993). The genus Eimeria comprises at least seven named species: E. tenella, E. necatrix, E. maxima, E. brunetti, E. acervulina, E. mitis and E. praecox. Of these, E. tenella and E. necatrix are the most pathogenic, followed by maxima and brunetti. Rose, M. E. and Long, P. L. “Vaccination against coccidiosis in chickens.” Vaccines against parasites (Eds.: A. E. R. Taylor, and R. Muller) Blackwell Scientific Publication, Ltd., Oxford, U.K. pp. 57-74 (1980). Infection with E. tenella and E. necatrix leads to hemorrhage and, in heavy infections, to anemia and death due to blood loss and shock.
Currently, two ways of controlling coccidiosis in chicken are available: chemical treatment with anticoccidial drugs and vaccination. Treatment with anticoccidial drugs has two important advantages: (1) it can be started directly after birth of the animal, and (2) it is cost-effective. There are also two important disadvantages: (1) an increasing level of resistance against various anticoccidial drugs is seen, and (2) there is an increasing reluctance towards the use of drugs from the point of concern about public safety.
Vaccination also offers a means of protecting against coccidial infection. Vaccination by mixing carefully determined small amounts of fully virulent strains with feed or drinking water is well known in the art. This method of vaccination is efficient but has some serious drawbacks: (1) the amount of oocysts given must be determined very carefully, and (2) animals that did not eat/drink enough at the day of vaccination become severely infected later on by the enormous amount of progeny oocysts that are produced when the vaccine strain recycles through the flock.
Vaccination with attenuated vaccines is also used in the art but only on a very modest scale. Such vaccines are highly amenable to reversion to virulence. Also, as a result of their attenuation, they suffer from severe loss of immunogenicity so that high numbers of oocysts must be given. Production thereof is, however, difficult and less cost-effective. Vaccination with subunit vaccines has not been shown to be sufficiently efficient so far.
Additionally, each vaccination unavoidably has the disadvantage that it takes at least 14-21 days before immunity builds up. Therefore, there is always a serious risk of infection in the days before the vaccination gives protection. And in practice, given the high infection pressure, this risk is too large to be taken.
Summarizing what is said about chemical treatment and vaccination, both can work but have their specific disadvantages. A combined treatment with both coccidiostatic drugs and vaccines comprises feeding coccidiostatic drugs the first few days combined with vaccination at the day of hatching seems attractive because the coccidiostatic drugs then only have to be used until immunity through vaccination has built up. This approach, however, is not easily feasible because the presence of the coccidiostatic drug kills not only infecting oocysts from the field but also the vaccine strains used to build up immunity.
A possible way out of this dilemma has been proposed in the Dutch Patent Application NL 8802399. In this application it was suggested to start as soon as possible with treatment with coccidiostatic drugs, followed by vaccination with specific Eimeria strains that are resistant against the coccidiostatic drug being administered.
Even these strains suffer, however, from drawbacks:
the strains used are not attenuated, therefore they are potentially dangerous; and
once introduced in the poultry industry, it is very difficult to remove these strains.
This is a serious problem since the strains are virulent and resistant at the same time. Large amounts thereof, as shedded after recycling through the flock, can easily infect subsequent groups of young birds kept in the same housing.